There has been a growing interest in the manufacture and use of microfluidic systems for the acquisition of chemical and biological information. In particular, when conducted in microfluidic volumes, complicated biochemical reactions may be carried out using very small volumes of liquid. Among other benefits, microfluidic systems are characterized by improved reaction response time, reduced sample volumes, and lower reagent consumption. When volatile or hazardous materials are used or generated, performing reactions in microfluidic volumes also enhances safety and reduces disposal quantities.
Traditionally, microfluidic devices have been constructed in a planar fashion using techniques that are borrowed from the silicon fabrication industry. Representative systems are described, for example, in some early work by Manz et al. (Trends in Anal. Chem. (1990) 10(5): 144-149; Advances in Chromatography (1993) 33: 1-66). In these publications, microfluidic devices are constructed by using photolithography to define channels on silicon or glass substrates and etching techniques to remove material from the substrate to form the channels. A cover plate is bonded to the top of the device to provide closure. Miniature pumps and valves can also be constructed to be integral (e.g., within) such devices. Alternatively, separate or off-line pumping mechanisms are contemplated.
More recently, a number of fabrication methods have been developed that allow microfluidic devices to be constructed from plastic, silicone or other polymeric materials. In one such method, a negative mold is first constructed, and plastic or silicone is then poured into or over the mold. The mold can be constructed using a silicon wafer (see, e.g., Duffy et al., Analytical Chemistry (1998) 70: 4974-4984; McCormick et. al., Analytical Chemistry (1997) 69: 2626-2630), or by building a traditional injection molding cavity for plastic devices. Some molding facilities have developed techniques to construct extremely small molds. Components constructed using a LIGA technique have been developed at the Karolsruhe Nuclear Research center in Germany (see, e.g., Schomburg et al., Journal of Micromechanical Microengineering (1994) 4: 186-191), and commercialized by MicroParts (Dortmund, Germany). Jenoptik (Jena, Germany) also uses LIGA and a hot-embossing technique. Imprinting methods in PMMA have also been demonstrated (see, Martynova et al., Analytical Chemistry (1997) 69: 4783-4789). These techniques, however, do not lend themselves to rapid prototyping and manufacturing flexibility. Moreover, the tool-up costs for both of these techniques are quite high and can be cost-prohibitive.
Laboratory processes including synthesis and analysis are characterized by numerous variables capable of affecting the results of the particular process. Considerable resources—in terms of labor, materials, equipment, and time—are expended in developing and optimizing new synthetic and analytical processes. Typically, a first experiment is performed according to a first set of process conditions, followed by performance of a another experiment with a slightly modified set of process conditions, followed by a performance of subsequent experiment(s) with further modified process conditions.
It would be desirable to reduce the expenditure of resources to develop and optimize new processes. In particular, it would be desirable to provide devices capable of subjecting similar samples or reagents to different process conditions in parallel. Ideally, such devices would utilize one or more common inputs from external devices such as pumps to minimize equipment cost. Additionally, such devices would be substantially non-reactive in the presence of various chemicals and substances, capable of withstanding elevated operating pressures, and economical to fabricate in small or large quantities.